Midterm 3 Bio A

Non-Mendelian Genetics

1) X-linked

2) Sex-linked

3) Multiple Alleles

4) Codominance

5) Incomplete dominance

6) lethality

Mendel’s Experiment

• Used pea plants

• Focused on flower color, seed shape, and pod color

• Law of segregation

• Law of independent assortment

• Traits are inherited as discrete genes

• Dominant traits can mask recessive ones

Law of segregation (Mendel)

During the formation of gametes, the two alleles for a trait segregate from each other

• each gamete only carries one allele for each gene

• Principle explains how offspring inherit one allele from each parent

• Results in genetic combinations

Law of independent assortment (Mendel)

• Alleles for different traits segregate independently of one another during gamete formation

• Inheritance of one trait will not affect the inheritance of another trait

• Only applies to genes located on different chromosomes or those far apart on the same chromosome

• Leads to genetic variation

Crossover

• occurs during meiosis

• Homologous chromosomes exchange segments of genetic material

• Exchange happens during prophase I

• Increases genetic diversity by allowing variations of traits to be passed on

• Leads to evolution and adaption

Relationship between Independent Assortment & Crossover

• Contribute to genetic variation during meiosis

• Independent = split without influencing other traits

• Crossover = exchange of genetic material

Linked Genes

• Located together on same chromosome

• Tend to be inherited together

• Do not assort independently

• Crossing over can break linkage

• The further the genes are from each other, the more likely a crossover event will happen

• Can have multiple crossover events

• 0-50% (Independent assortment max is 50%)

Explain how crossover happens

• Occurred during meiosis I (specifically during Prophase I)

• Synapsis

  • Homologous chromosomes must find each other (one from each parent) before crossing over can happen

  • They line up side-by-side, gene-by-gene

  • Tight pairing is called synapsis

  • Held together by protein structure (synaptonemal complex)

• Chiasmata Formation

  • Once paired, the non-sister chromatids (one from each parent) overlap at specific points

  • Contact points called chiasmata

  • This is where actual break and swap happens

• DNA swap

  • specialized enzymes break the sugar-phosphate backbone of the DNA at the same location on both non-sister chromatids

  • Broken segments re-sealed to the opposite strand

• Genetic Recombination

  • As meiosis continues, the homologous chromosomes are pulled apart

  • Recombinant chromosomes

Allele

• Specific variation of gene

  • Gene —> general characteristic —> alleles → determine specific expression of trait

• Found on locus

• Homozygous

• Heterozygous

• Dominant

• Recessive

Polygenic Traits

• Polygenic inheritance controlled by 2+ genes

• Creates a continuous gradient (bell curve)

• Each dominant allele “adds” a small amount of phenotype

  • skin

  • height

  • eyes

Pleiotropy

• One single gene influences multiple traits

• Usually happens because the gene codes for a protein that is used by many different types of cells throughout the body

Synergistic genes

• Synergistic interactions results in more intense phenotype (polygenic)

• happens because the genes are part of the same metabolic or signaling pathway

• Often, a certain trait won't appear at all until a specific combination of synergistic genes is present

Epistasis

• When the effect of one gene is hidden or masked by the presence of a different gene

• one gene overriding

• gene that does the masking is called epistatic

• the gene being masked is hypostatic

• usually happens because the epistatic gene controls a step that occurs earlier in a biological pathway

Recessive Epistasis

• two copies of the "masking" allele to hide the other gene

Dominant Epistasis

• one copy of the "masking" allele to hide the effects of the other gene

Monohybrid Cross

• Tracks the inheritance of one single trait

• 3:1 (phenotype)

• 1:2:1 (genotype)

Dihybrid Cross

• tracks the inheritance of two independent traits simultaneously

• 9:3:3:1 (Phenotype)

Test Cross

• discover the unknown genotype of an individual showing a dominant phenotype

Self Cross

• occurs when an individual is crossed with itself or

• with an individual of an identical genotype

Pedigree Analysis

• visual chart (a "family tree") that tracks the inheritance of a specific trait through multiple generations

• can determine if the gene is dominant or recessive and if it is located on an autosome or a sex chromosome

• Autosomal dominant: every generation rule; males and females with similar frequency

• Autosomal recessive: Unaffected parents can have affected children (meaning the parents are "carriers")

• X-linked

X-Linked Dominant

• If a father is affected, all of his daughters will be affected, but none of his sons

• An affected mother has a 50% chance of passing it to any child

Hemizygous

• describes an individual who has only one copy of a particular gene or chromosome segment, instead of the usual two

• we inherit two alleles for every autosomal gene, if one copy is missing—either naturally or due to a deletion

Sex Chromosomes

Females: XX
Males: XY (hemizygous) - fewer genes (shorter)

• Y has a region similar to x for meiosis

Multiple alleles

Wild type (+) → Dominance; refers to phenotype/genotype most commonly observed

Variants (-) → differs from wild type

• If variants becomes common (>1%) then it becomes a polymorphism

Dominant hierarchies

• forms when multiple alleles exist in a population

• the alleles are ranked by their ability to mask one another

Codominance + Blood type

• equal expression of alleles

• Blood types:

  • Type A: people have A antigens → anti-B antibodies

  • Type B: people have B antigens → anti-A antibodies

  • Type AB: people have both equal parts A and B antigens → no antibodies → Universal acceptor

  • Type O: people have no antigens → have both A and B antibodies → universal donor

• Rh Factor (follows normal mendelian)

  • + → have protein (dominant)

  • - → no protein (recessive) - produce protein to attach Rh protein

Incomplete dominance

• intermediate blend

• dominant allele isn't strong enough to fully mask the recessive one

• the heterozygous offspring ends up with a "diluted" version of the trait

• Most times the recessive allele is a loss of function allele

• Genotypes: 1:2:1

• Phenotypes: 1:2:1

• Snapdragons

  • the plant produces the full amount of red pigment (dominant)

  • recessive produces no red pigment, flowers are white

  • Pink flower

Lethality

• refers to a situation where a specific combination of alleles is so disruptive to an organism's development or survival that it results in death

• usually happens because the gene involved is essential

• organism only dies if it inherits two copies of the lethal allele (homozygous recessive)

  • Carriers: may show a distinct phenotype that looks like a dominant trait

• Only one copy of the allele is needed to cause death, allele isn’t passed on

  • lethal effect doesn't kick in until after reproductive age (like Huntington’s Disease in humans), the allele can persist in a population

a) A and W 

b) G and R

c) W and E

d) E and G

C

A series of dihybrid crosses are done between Labrador dogs with black coats. The ratio of phenotypes of the offspring is found to be 9 black to 3 brown to 4 yellow coat color. This ratio of phenotypes results from _____.

a) gene linkage

b) codominance

c) incomplete dominance

d) epistasis

D

A homozygous plant with red flowers is crossed to a homozygous  plant with white flowers and three phenotypes are observed among the offspring in the following ratios: 1 red to 2 pink to 1 white. The ratio of the phenotypes of the offpsring of this cross is likley caused by _____.

a) incomplete dominance of the red allele.

b) gene linkage between the red and white alleles.

c) Mendelian dominance of the white allele.

d) epistasis of the white allele

A

If you cross two heterozygous organisms and observe that the ratio of three offspring phenotypes is 1 to 2 to 1 then the ratio can only be the result of two codominant alleles. (T or F)

F

Based on Figure 12.8 and the paragraph immediately preceding the figure, you crossed two rabbits with Himalayan fur to each other and observed that the ratio of the offspring was 3 Himalayan fur to 1 albino fur. What must be the genotypes of the two parents?

a) c^hc^h and cc

b) c^hc and c^hc

c) cc and cc

B

Linkage

• Less than 50% new recombinants

• Reduced crossover

• Use test cross to see linkage by using phenotypic ratio and summing the recombinants, and dividing over total DNA

• Gives distance and order of genes (ex 17% crossover = 17 map units)

Unlinked

• Mendelian 1:1:1

• Expect 50% novel allele combos

• Half parental, half recombinant

Cell cycle

• Interphase: cell grows and DNA is replicated - DNA semi-condensed

  • G1

  • S

  • G2

• Mitotic: replicated DNA and cytoplasmic contents are seperated

  • PMAT

Interphase

• G1: Cell accumulates building blocks of chromosomal DNA, proteins, and energy

• S: Formation of identical pairs of sister chromatids attached at centromere; centrosome duplicated → mitotic spindle

  • Centrioles (rod-like) + centrosomes

• G2: Cell replenishes its energy stores and synthesizes proteins necessary for chromosome movement

  • Cell organelles duplicated

  • Cytoskeleton dismantled

  • Final prep

• G0: Cells not actively dividing

  • Environment

  • Will stay until improved or triggered

Mitotic

PMAT

• Prophase

  • Nuclear envelop dissociates

  • Membranous organelles

  • Nucleolus disperses

  • Centrosomes move to opp ends

  • Sister chromatids coil more tightly with aid of cohesin proteins

• Prometaphase

  • Nuclear envelope fragments

  • Mitotic spindle continues to develop as more microtubules assemble and stretch

  • Each sister chromatids develops kinetochore in centrometric region

  • Chromosome oriented until the kinetochores of sister chromatides face opposite ends

    • Spindles that do not engage are called polar microtubules

  • Microtubules overlap midway b/w 2 poles and contribute to cell elongation

• Metaphase

  • All chromosomes align along metaphase plate

  • Sister chromatids are sitll tightly attached by cohesin proteins

  • Chromosomes maximally condense

• Anaphase

  • Cohesin proteins degrade

  • Sister chromatids separate at the centromere

  • Chromatid = single chromosome

  • chromosomes pulled rapidly toward the centromere

  • cell elongates

• Telophase

  • Chromosomes reach opposite poles and begin to decondense

  • Relaxed in stretched-out chromatin configuration

  • Mitotic spindle depolymerized into tubulin monomers

    • Will be used to develop cytoskeletal components for each daughter cell

Cytokinesis

• optional - if doesn’t happen then daughter cells are multi-nucleated

• Physical seperation of daughter

• Animal cell:

  • starts in late anaphase

  • contractile ring composed of actin filaments forms inside the membrane

  • Actin filaments pulls the equator of the cell inward forming a fissure (cleavage furrow)

  • Furrow depends a the actin ring contracts

• Plant cell:

  • new cell wall forms

  • during interphase, the golgi apparatus accumulates enzymes, structural proteins, and glucose propor to breaking into vesicles and dispersing throughout the dividing cell

  • telophase: golgi vesicles fuse and coalesce from the center to walls

  • as more fuse, gets longer

Internal checkpoints

• Near end of G1: DNA damage, cell size, adequate reserves; cell fix, G0 until triggered or improved

• G2/M: All chromosomes replicated/DNA damaged; complete DNA replication OR try to fix damage

• Metaphase: Determines whether all sister chromatids are anchored to at least 2 spindle fibers from opposite sides

External regulators

• apoptosis

• human growth hormone (HGH)

  • Lack of HGH: inhibit proliferation (dwarfism)

  • Too much of HGH: excessive proliferation (gigantism)

• Crowding of cells could inhibit proliferation

• If a cell becomes too big, and starts to lack in nutrients, will divide

Regulator molecules

• For the cell cycle to continue:

  • All positive regulators on

  • All negative regulators off

• Regulator molecules may act independently, influence activity or production of other regulatory proteins

Positive Regulation

Promotes progress

• cyclins

• Cdks

Cyclins & Cdks

• Cdks are enzymes (kinases) that phosphorylate other proteins (shape change)

• Cyclins regulate cycle when tightly bound to Cdks

• 4 cyclin proteins fluctuate based on timing of cycle

• Cdk concentration is constant, what changes is whether it’s active or not

1) Specific cyclin binds to Cdks, promoting Cdk shape change

2) Cdk → target protein - takes p from ATP and attaches to protein

3) Target protein shape change

4) Cyclin degrades

Cyclin Fluctuation Throughout Cell Cycle

1) Once G1 initiated, cyclin D synthesized and drives the G1/S phase transition

• Rb phosphorylates, bound to E2F

2) Rb releases E2F which starts transcription of cyclin E which fully phosphorylates Rb

3) Cylclin E produces p27 which inhibits cyclin D

• Phosphorylation of p27 tags it for degradation

4) Degradation promotes production of cyclin A by remaining CCRE from promotor (negative feedback) allowing it to enter S phase

• E2F on cyclin A is part negative feedback loop

• Cyclin A + CDK2 complex phosphorylates E2F, preventing from removing suppressor

5) Cyclin B → Maturation-Promoting Factor (MPF) → cells exit M phase

Negative Regulation

• Cdk inhibitors: can trigger apoptosis

  • Rb (retinoblastoma protein): tumor-suppressor proteins

  • p53: if damaged, halts cell cycle and recruits specific enzymes to repair DNA, tumor-suppressor

  • p21: enforces the halt in the cycle by binding to and inhibiting cyclin/Cdk complexes

    • increase of p53 triggers production of p21

• These all act primarily at the G1 checkpoint

retinoblastoma protein (Rb)

• largely monitors size

• inactive, dephosphorylate Rb binds to TF (E2F)

  • Rb → E2F, production of proteins for G1/S block

  • Increase in size, Rb becomes inactive and releases E2F

p53

1) DNA damage activates kinases that phosphorylate p53

2) Phosphorylated p53 turns on genes that inhibit cell cycle

• Helps repair DNA after G1 phase (before it replicates DNA in S-phase)

3) Inhibiting the cell cycle gives the cycle time to repair the damaged DNA

2 Hit Hypothesis

• Both copies of a tumor suppressor gene must lose function for cancerous phenotype to develop

• 2 mutations = 2 hits for cancer to develop

• If have one copy, the second copy could later develop

• Hereditary: passed two copies down

• Nonherediatry (sporadic): Normal → develops one mutated tumor suppressor → the other one develops

Cell Signaling Pathways

• MAPK/ERK

• Wnt

• Both increase cyclin D

MAPK/ERK

• MAPK (Mitogen-activated protein kinase)

• Activated by TGF(alpha) → EGFR regulates (growth factor receptor) through sos/Grb2 → activates Ras

• Cascade: Ras → B Raf → MEK ½ → Erk ½

• Erk once activated translocates to nucleus, activating several genes and TF

  • c-myc, Ets, c-Jun, c-fos → all relate to cell proliferation, survival, and metastasis

c-myc

• proto-oncogene, may become an oncogene

• only need 1 copy mutated for mutation

  • excess amounts: codes for proteins that increase proliferation

3 oncogenic mutations

1) Mutation/Deletion - proteins with increased function

2) Gene duplication - more copies

3) Translocated enhancer/promoter increases transcription - more copies

Immediate Early Genes (IEG)

• c-fos, Elk-1

• ERK immediately phosphorylates c-Fos and Elk-1 because they don’t require new protein synthesis to be activated

Normal protein

• Regulatory: allow to make protein when needed

• Proto-oncogene: need to replicate

Wnt Pathway

• On: beta-Centenin goes inside nucleus to tell it to divide

• Off: Proteosome, no gene transcription for division

During which phase of the cell cycle does DNA replication occur?

 

a) G₁

 

b) S

 

c) G₂

 

d) G₀

b

Sister chromatids are pulled apart by mitotic spindle fibers during which phase of mitosis?

 

a) Prometaphase

 

b) Metaphase

 

c) Prophase

 

d) Anaphase

d

The phase of mitosis in which the nuclear envelope re-forms in preparation for cytokinesis is called _____.

 

a) prophase

 

b) metaphase

 

c) telophase

 

d) prometaphase

c

Which statement about cyclins is FALSE?

 

a) Cyclins are positive regulators of the cell cycle

 

b) Cyclin concentrations rise and fall throughout the cell cycle

 

c) Cyclins bind to CDKs

 

d) Cyclins phosphorylate target proteins

d

What is the normal function of Rb?

 

a) Rb is a positive regulator of the cell cycle

 

b) Rb phosphorylates target proteins

 

c) Rb activates transcription of multiple genes

 

d) Rb inhibits progression through the cell cycle

d